Phospholamban gene dosage effects in the mammalian heart
Phospholamban gene dosage effects in the mammalian heart
复制标题
DOI：
10.1161/01.res.78.5.839
复制
发表时间：
1996-05-01
影响因子：
20.1
通讯作者：
Kranias, EG
中科院分区：
文献类型：
--
作者：
Luo, WS;Wolska, BM;Kranias, EG
已显示受磷蛋白消融导致心脏收缩参数显著增加和β-肾上腺素能刺激丧失。为了确定受磷蛋白水平的部分降低是否也与心脏性能的增强相关，并进一步检查收缩系统对受磷蛋白水平改变的敏感性，在亚细胞、细胞和器官水平平行研究了来自野生型、受磷蛋白杂合型和受磷蛋白缺陷型小鼠的心脏。与野生型小鼠相比，受磷蛋白杂合小鼠表达的心脏受磷蛋白mRNA和蛋白水平降低（40+/-5%）。受磷蛋白水平降低与肌浆网Ca 2+泵对Ca 2+的EC（50）显著降低以及分离的心肌细胞和跳动心脏的收缩参数增加相关。野生型、受磷蛋白酶杂合型和受磷蛋白酶缺陷型小鼠心脏中受磷蛋白酶的相对水平与（1）肌浆网中Ca 2 +-ATP酶对Ca 2+的EC（50）、（2）离体心肌细胞的舒张和收缩速率以及（3）完整跳动心脏的舒张和收缩速率相关。这些发现表明受磷蛋白水平的生理和病理变化将导致肌浆网功能和心脏收缩的平行变化。
Phospholamban ablation has been shown to result in significant increases in cardiac contractile parameters and loss of beta-adrenergic stimulation. To determine whether partial reduction in phospholamban levels is also associated with enhancement of cardiac performance and to further examine the sensitivity of the contractile system to alterations in phospholamban levels, hear ts from wild-type, phospholamban-heterozygous: and phospholamban-deficient mice were studied in parallel at the subcellular, cellular, and organ levels. The phospholamban-heterozygous mice expressed reduced cardiac phospholamban mRNA and protein levels (40+/-5%) compared with wild-type mice, The reduced phospholamban levels were associated with significant decreases in the EC(50) of the sarcoplasmic reticulum Ca2+ pump for Ca2+ and increases in the contractile parameters of isolated myocytes and beating hearts. The relative phospholamban levels among wildtype, phospholamban-heterozygous, and phospholamhan-deficient mouse hearts correlated well with the (1) EC(50) of the Ca2+-ATPase for Ca2+ in sarcoplasmic reticulum, (2) rates of relaxation and contraction in isolated cardiac myocytes, and (3) rates of relaxation and contraction in intact beating hearts. These findings suggest that physiological and pathological changes in the levels of phospholamban will result in parallel changes in sarcoplasmic reticulum function and cardiac contraction.